Berberine displays antitumor activity in esophageal cancer cellsin vitro

Abstract

AIMTo investigate the effects of berberine on esophageal cancer (EC) cells and its molecular mechanisms.METHODSHuman esophageal squamous cell carcinoma cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used. The effects of berberine on cell proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. For cell cycle progression, KYSE-70 cells were stained with propidium iodide (PI) staining buffer (10 mg/mL PI and 100 mg/mL RNase A) for 30 min and cell cycle was analyzed using a BD FACSCalibur flow cytometer. For apoptosis assay, cells were stained with an Annexin V-FITC/PI apoptosis detection kit. The rate of apoptotic cells was analyzed using a dual laser flow cytometer and estimated using BD ModFit software. Levels of proteins related to cell cycle and apoptosis were examined by western blotting.RESULTSBerberine treatment resulted in growth inhibition of KYSE-70 and SKGT4 cells in a dose-dependent and time-dependent manner. KYSE-70 cells were more susceptible to the inhibitory activities of berberine than SKGT4 cells were. In KYSE-70 cells treated with 50 μmol/L berberine for 48 h, the number of cells in G2/M phase (25.94% ± 5.01%) was significantly higher than that in the control group (9.77% ± 1.28%, P < 0.01), and berberine treatment resulted in p21 up-regulation in KYSE-70 cells. Flow cytometric analyses showed that berberine significantly augmented the KYSE-70 apoptotic population at 12 and 24 h post-treatment, when compared with control cells (0.83% vs 43.78% at 12 h, P < 0.05; 0.15% vs 81.86% at 24 h, P < 0.01), and berberine-induced apoptotic effect was stronger at 24 h compared with 12 h. Western blotting showed that berberine inhibited the phosphorylation of Akt, mammalian target of rapamycin and p70S6K, and enhanced AMP-activated protein kinase phosphorylation in a sustained manner.CONCLUSIONBerberine is an inhibitor of human EC cell growth and could be considered as a potential drug for the treatment of EC patients.

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…Berberine has diverse pharmacological effects and is normally used for the treatment of gastroenteritis [133,134]. It exhibits significant anti-cancer effects in a wide spectrum of cancers including ovarian, breast, esophageal, and thyroid cancers, leukemia, multiple myeloma, nasopharyngeal carcinoma, and neuroblastoma, through inducing cell cycle arrest and apoptosis, inhibiting metastasis and angiogenesis [135][136][137][138][139][140][141][142][143].…”

Berberine induces mitochondrial‑mediated apoptosis and protective autophagy in human malignant pleural mesothelioma NCI‑H2452 cells

“…Berberine has extensive pharmacological effects, including anti-hypertensive, anti-diabetic, anti-arrhythmia and anti-hyperlipidemic (3)(4)(5)(6). Recent studies have shown that berberine exerts antitumor effects in a variety of human cancer cells, such as breast cancer, hepatocellular carcinoma, leukemia, and esophageal cancer, both in vitro and in vivo, by suppressing proliferation, inducing apoptosis, arresting the cell cycle, and inhibiting invasion and metastasis (7)(8)(9)(10)(11)(12). In addition, it has been recently reported that berberine-induced autophagy has been observed in hepatic and colon cancer cells (13,14).…”

Preventive and Therapeutic Roles of Berberine in Gastrointestinal Cancers

“…Furthermore, many studies have shown that BBR can be used for treating hypertension, cardiovascular diseases (due to antiheart failure, antiarrhythmia, and antiplatelet aggregation effects), neuronal diseases, gastrointestinal disorders, and several types of cancers [6][7][8][9][10]. e molecular and cellular mechanisms underlying the therapeutic effects of BBR, such as anti-inflammatory, antiapoptotic, antioxidative, and autophagy-promoting activities, have been found to involve some signaling pathways, such as the mitogen-activated protein kinase (MAPK) signaling, phosphatidylinositol-3 kinase/AKT/mammalian target of rapamycin (PI3K/Akt/mTOR), the Janus Kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), and the nuclear factor erythroid 2-related factor 2/hemeoxygenase-1 (Nrf2/HO-1) pathways [11].…”